1. Field of the Invention
This invention is in the field of electroporosis, and relates in particular to time domain methods for generating electromagnetic fields in the interior of the body to improve delivery of therapeutic drugs to the body's cells.
2. Description of the Prior Art
Electroporosis is the process wherein cell membrane pores are opened through the application of electromagnetic fields. For example, Dr. Diane Gaylor of MIT has demonstrated electroporosis of normal skeletal muscle cells at electric field gradients as low as 2.5 kV per meter. Inoperable cancers are frequently treated by chemotherapy, ionizing radiation, or combined radiation/chemotherapeutic modalities. A central limitation of chemotherapeutic effectiveness is the inability of the chemical agent to penetrate into the tumor tissue, and especially into the tumor cell, thus resulting in resistance to therapy. Dr. Mir in France has experimentally determined that electroporation of cancer cells can increase the influx of chemotherapeutic agents into those cells by more that 50 fold. He has also demonstrated that this effect appears useful in treatment of human patients with inoperable cancer in cases where electrodes can be placed on the skin on opposite sides of the tumor. In these treatments the patient is pre-loaded with an orally administered chemotherapeutic agent and the locally imposed electromagnetic field is believed to increase tumor uptake of the agent through the process of membrane electroporation.
Other diseases suffer the same difficulty of getting the therapeutic drug to the target site. For example, diseases based on the existence of intracellular organisms, such as viruses or parasites, are frequently resistant to drug therapy because of failure of the medicine to penetrate the cells. Other examples include the inability of AZT to penetrate the immune cell in the treatment of AIDS, the difficulty in treating another viral ailment, cytomegalic inclusion disease, and Chagas disease, a parasitic infestation.
While electrodes have been used to generate sufficient electromagnetic fields for electroporosis near the surface, they can not effectively reach tumors deep within the human body. Electrodes can easily be used when the tumor is superficial. However, electrodes require surgical procedures if they are to be used within the body.
U.S. Pat. No. 5,386,837 teaches a method of applying pulses of high-frequency force fields (rf, microwave, high-energy infrared, laser electromagnetic wave energy, or ultrasonic acoustic energy) to portions of the human body for the purpose of making those portions more susceptible to chemotherapeutic drugs. One or more applicators deliver energy such that at the site at which these beams intersect, the intensity is sufficient to open the cell.
The '837 patent differs from this invention in several ways. The cited patent uses heat inducing sources. The present invention uses ultra-wide band (UWB) sources that are polarized time domain pulses that locally raise the field strength in the region of a tumor to a level sufficient to induce electroporosis. The use of UWB pulses also inherently provides for very low rf energy being used to induce electroporosis, the energy being limited to that associated with short pulses on the order of picoseconds to nanoseconds. This avoids tissue heating. The use of UWB pulses at a very low pulse repetition frequency also avoids osmotic shock, the rupture of cells when exposed to high field strength or too much exposure. Holding the cell walls open can result in an inability to close the pore and results in cell rupture.